Alexza Inhaled Antipsychotic May Pose Fatal Lung Risks

Dec. 7 (Bloomberg) -- Alexza Pharmaceuticals Inc.’s inhaled
antipsychotic drug may put some patients at risk for respiratory
failure, according to U.S. regulators considering whether to
approve the treatment for sale.

While Adasuve is effective as a fast-acting treatment for
agitation among patients with schizophrenia and bipolar
disorder, it can cause bronchial spasms that may be fatal in
people with conditions such as asthma, Food and Drug
Administration staff said today in a report. Outside advisers to
the agency plan to meet Dec. 12 to evaluate the findings.

Adasuve would be the first product for Mountain View,
California-based Alexza. The therapy uses an inhalation device
developed by the company to deliver a vaporized form of the
antipsychotic medication loxapine to the lungs for rapid
absorption into the bloodstream. The FDA aims to decide on the
product by Feb. 4.

“It is likely that, even with adequate screening for
pulmonary risk factors, some patients will require respiratory
support post-dose, and some patients will be at risk for
respiratory failure and death,” FDA staff said.

The drug, if approved, should only be administered by
professionals who have intubation tubes and ventilators
“readily available,” according to the report.

Adasuve failed to win FDA approval in October 2010, because
the agency was concerned about risks of pulmonary toxicity,
particularly in patients with asthma or chronic obstructive
pulmonary disorder.

Risk Mitigation Plan

Alexza resubmitted its application in August with a
proposed risk-mitigation strategy that includes screening
patients to identify those at risk for lung problems and
monitoring people who take Adasuve for an hour after treatment.

Those proposals didn’t resolve FDA reviewers’ concerns
because it may be difficult for health-care providers to monitor
psychiatric patients for early signs of bronchial spasms, the
report said.

“Psychotic and agitated patients who develop respiratory
symptoms may not be able to notify health-care personnel in a
timely manner, and respiratory distress may be confused with
acute agitation to the casual observer,” agency staff said. The
drug’s sedating effect “may also mask respiratory signs and
symptoms while causing further respiratory suppression.”

The FDA asked its Psychopharmacologic Drugs Advisory
Committee to weigh in on Adasuve’s effectiveness and safety, and
on whether Alexza’s risk-mitigation proposal is sufficient to
ensure the benefits of the drug justify its risks.

A company-funded study published in January in the British
Journal of Psychiatry found that Adasuve started to work within
10 minutes of inhalation and was more effective than a placebo
in cutting agitation levels within two hours.

There haven’t been any studies directly comparing Adasuve
with other drugs approved to treat agitation in patients with
schizophrenia and bipolar disorder, the FDA reviewers said.